L. Stephen Coles, M.D., Ph.D., is the Director and a co-founder of the Gerontology
Research Group in Los Angeles. He is a stem-cell researcher in the Department of Surgery at the
UCLA Geffen School of Medicine. In addition, he has organized a lecture series in gerontology
for the past 12 years. He formerly taught Computer Science and Artificial Intelligence at UCLA,
the University of Southern California, and the California Institute of Technology. Previously, he
taught at Stanford University and at UC Berkeley, where he introduced the first graduate course
in robotics in 1973. He received his bachelor’s degree in electrical engineering from
Rensselaer Polytechnic Institute in Troy, NY, pursued graduate work in mathematical statistics at
Columbia University, and received an M.S. in mathematics and a Ph.D. in systems and
communication sciences from Carnegie-Mellon University. Later, Dr. Coles attended Stanford
Medical School and did his Clinical Internship in Obstetrics/Gynecology at the University of
Miami Jackson Memorial Hospital. He is a founding member of the JAAM Editorial
Board.

Dr. Coles, please provide a brief historical perspective
of the Gerontology Research Group (GRG). When and how was it founded and what were its
initial mission and goals?

Dr. Steven Kaye, M.D., and I
co-founded the GRG during the spring of 1990. We met once a month for about six months in
each other’s homes and along the way wrote a Charter, or Mission Statement, for the
group, describing what we wanted to see done in our lifetimes in the field of Anti-Aging
Medicine. We kept adding to our list based on what we knew might become possible someday.
Steven was a family physician in private practice who, at that time, owned a series of clinics in the
Los Angeles area. Then a third person joined us, Dr. Robert Nathan, Ph.D., from the
Jet Propulsion Lab (JPL/CalTech), who was also interested in

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L. Stephen Coles, M.D., Ph.D.

Co-Founder, LA-GRG

experimental gerontology and attended our monthly
meetings for another four or five months. A fourth
member, Bernard L. Strehler, Ph.D., Professor of
Biology at the University of Southern California, then
joined our group. Soon, Steven Harris, M.D., from
Roy Walford’s team at UCLA, joined us. From there,
the group rapidly expanded to about 15 regular
members.

We started asking extremely detailed
questions
about what we thought would be feasible within what
time frame, recalling that we wanted to achieve
something useful in our own lifetimes. We quickly
realized that, as a group,

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we did not have
enough information, so we contacted
two graduate students of a well-known Professor of
Chemistry at CalTech to give us a lecture on their
research involving the direct sequencing of DNA using
an Atomic-Force Microscope. We suspected that if we
better understood DNA sequencing, we would be on a
critical path to understanding the future of Anti-Aging
Medicine. That talk, in January of 1991, was our first
formal lecture, and since then we have had at least one
lecture per month for the past 12 years (including
Summers) — 154 lectures and still going strong! In
retrospect, our presenters have included world-famous
researchers in gerontology. We videotaped each lecture
and now have an extensive library of VHS tapes. Over
the years we have also taken a half-dozen field trips to
look at different labs (including some now-defunct
clinics in Mexico).

In recent years, our lectures have been
mostly held
in a standard lecture hall at the UCLA Medical School,
but at least once a year we meet at CalTech and at
USC. For any given lecture, 15 to 20 persons typically
attend. About half the lectures are clinical in nature,
while the other half focus on the basic sciences (or
sometimes on engineering instrumentation), in which
we talk about the chemistry and physics of molecular
processes in the body. About half of our members are
Ph.D.’s and about a quarter are M.D.’s. After each
lecture, I generally review the latest news
developments in gerontology and medicine.

Today, the Los Angeles Gerontology
Research
Group consists of about 160 members: we have also
founded Chapters in other cities, such as Washington,
D.C. and New York City. About six years ago, we
established a website (www.grg.org) which is filled
with various sorts of resources for teaching
gerontology, including “Breaking News” and
“Editorial Opinions,” particularly about stem cells. It
contains a master list of all of the previous lectures and
summaries of the backgrounds of the lecturers. More
recently, we have established a Gerontology
Discussion Group associated with the GRG (a sort of
loosely moderated Internet Chat Room) that has over a
hundred members worldwide. It is impossible to
predict when I might say something quite innocently,
such as, “Aging should no longer be thought of as a
disease,” and that

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could result in a five-week multi-part discussion with
many sub-threads running in parallel. Although there
are a number of frequent contributors to these
discussions, most subscribers remain as quiet observers
with what I suspect is amusement or bewilderment
while these intense discussions are taking place.

We wrote the original Charter for our
organization
in the Fall of 1990. We have modified it slightly, with
the consent of the members, maybe ten times over the
past 10 years, but only to dot an “i” or cross a “t” here
and there. There have been remarkably few changes
made in emphasis and only occasional insertions of
new jargon as it becomes fashionable; otherwise, the
basic mission of the GRG remains the same as it did a
decade ago — to discover the technical means for
intervention in the human aging process within our
lifetimes.

How does the group go about meeting those goals?

One of the continuing interests of the
group is to
authenticate cases of the oldest humans in history, the
population of so-called Supercentenarians (persons
greater than 110 years old). We publish the most
current list of living Supercentenarians on a bimonthly
basis in this Journal of Anti-Aging Medicine. In 1998,
we began to compile and publish this list on our
website. We also maintain a photo gallery of over 100
pictures of these individuals, which are sent to us as E-mail attachments by interested relatives and
nursing-
home administrators.

Our interest in this population began
when we
established a collaboration with the Chairman and Co-Chairman, located in New York and
Atlanta, Georgia,
respectively, of the International Supercentenarian
Committee. This Committee consists of approximately
30 demographers and epidemiologists with
representatives in each major country of the world. We
communicate, seven days a week, almost exclusively
by E-mail. We strive to maintain the list of
Supercentenarians as accurately as possible. In order
to create our database of the world’s oldest people, we
established rigorous criteria for entry. Many
unscrupulous individuals

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(or their friends/family members) have claimed to be
very very old while, in fact, we regularly uncover
fraudulent claims — people who have tried to get into
The Guinness Book of Records, for example, as being
acknowledged as the world’s oldest living person.
Sometimes there is a more mundane motive, such as
having avoided military service when they were
younger. A young man could sometimes impersonate
his father, if he had the same first and last name, and
could use his Birth Certificate and/or Passport.
Because old age is venerated in some cultures, there
was no incentive to switch back at a later time. But
such claims are obviously invalid, and we have taken it
upon ourselves to do the investigative work to identify
and expose these fraudulent cases whenever we can.

In order to be included in our official
database, a
person needs to have at least three independent sources
of documentation: a Birth Certificate, Baptismal
Certificate, or Marriage Certificate; consistent US
Census records dating back to 1900; and some other
photo identification, such as an old driver’s license. A
handwritten entry in a family bible is not sufficient.
We have even seen one case in which a person’s birth
was recorded in a family bible, but the bible was not
even published until four years after the stated birth
date! We include persons from all over the world, so a
lot of our documentation is in various foreign
languages, and we therefore require country-specific
translators. All of our committee members offer their
services on a volunteer basis. We have representatives
in many countries, including all of the major European
countries, Mexico, Canada, Japan, and Australia.
Although we do not yet have anyone in China or India,
we are actively working on that and hope to have new
members from these countries before next year’s end.

We routinely collect and scan into our
database all
of the documents we require. We record the person’s
full name (maiden and married), birth date, the country
or state (in the U.S.) where they were born, the
country/state where they currently reside, and the name
of the committee member who was responsible for
endorsing the validity of the documents. Thus, we
have become a de facto world authority on the

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authentication
of Supercentenarians, without ever
planning to take on such a role. As a result, we are
regularly contacted by historians and journalists. We
have discovered that there are a large number of
obituary columnists in every city in the U.S. who write
the human-interest side of obituaries of persons who
have lived for an unusually long time, not just those
who lived in their local area. Today, when one of our
Supercentenarians dies, we get calls from the major
wire services (AP, Reuters, etc.) and from journalists
all over the world who want to know whether this
individual was really the age that was claimed by their
family. The Guinness Book of Records now cites us, as
well, as a world authority for this type of factual
information.

Do you collect any types of information related to
family history or medical history, or solely
demographic data?

So far, the database we publish on our
Internet
website contains strictly demographic data, along with
statistical tables of interest to epidemiologists. For
example, we recently got a call from a physician with
the Social Security Administration who wanted to
know how to cut down on fraud from within their own
database by calculating the probability that someone in
the US of a given claimed age was likely to be alive.
Ultimately, however, we hope that this data will
become a resource for exploring scientifically
interesting questions about what these very old people
have in common. When I interview the
Supercentenarians who live in the U.S., I
systematically videotape the interviews and try to learn
everything I can about each person’s family history,
their medical history, their lifestyle, nutrition, exercise,
occupation, religion, etc. Based on the information we
have gathered, I can safely testify that these people
have virtually nothing in common, other than their
parents having lived a long time (if they did not die of
a traumatic injury or in a flu epidemic); however, their
spouses generally do not. We can say that their siblings

(and their children) tend to live a long time as well. So
there is something going on in the genes that could
explain the inheritance of longevity, but we do not
know what that is yet.

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When people ask us what they themselves can do to
live a long time, the answer is “the dice were already
rolled when your genes were determined by your
parents.” Many of our Supercentenarians lived what
we, today, would call an “unhealthy lifestyle.” One
woman who smoked heavily most of her life, and
whose doctor had told her over and over that smoking
was bad for her, continued to smoke because she liked
to. She was also fond of pointing out that she had
outlived several of her doctors.

One of the more humiliating
conclusions that I can
share with our physician readers is that, as a
profession, physicians have virtually no claim to being
able to extend the maximum human lifespan, even
though they certainly do regarding the extension of
average life expectancy (for the population as a
whole). Obstetricians, pediatricians, infectious disease
specialists, and public health practitioners as a group
do have an important claim, as they collectively have
added nearly 30 years to the average life expectancy at
birth over the last century, and tripled it since Roman
times. But doctors in general are helpless in the face of
maximum lifespan, since most of the
Supercentenarians in our database never saw a doctor
until they were 90, especially those who were born in
rural areas. They never needed to, because they were
always so very healthy. They had no “weak link,” so
to speak, in their physical makeup. Also, they never
did anything risky enough to cause themselves to be
“taken out of the game” by repeated traumatic injury.
Thus, it is very complex to try and predict what
component of your personal lifestyle will help you to
live an extremely long time, once you state the obvious
precautions, such as “wearing a seat belt.”

But this does not invalidate in any way
the routine
recommendations that doctors and dentists make when
they tell their patients to exercise, floss their teeth, take
vitamins, not smoke, be scrupulous about not over-indulging in alcohol, and so forth. We do see
clear
lifestyle differences in longevity in laboratory studies
with mice, which are our close cousins as mammals.
However, people who are lucky in their genetic
makeup can get away with a bad lifestyle (including
smoking and drinking heavily) and still live a long
time. I would like

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to make it very clear that they do not live a long time
because of smoking and drinking heavily. No doctor
should recommend that you follow the lifestyle of
Supercentenarians in order to try and emulate them.
That may be a tempting, seductive trap; the real secret
lies in their genes and in not inheriting a “weak link.”

If we are going to learn anything about
the
inheritance of super-longevity, we are going to have to
identify the genes that control the aging process itself.
Chromosome 4 seems to be an attractive candidate, but
a cholesterol-aggregation gene recently discovered by
researchers in New York looks promising. Formal
medical studies are underway in the Boston area,
where one of our colleagues, Dr. Tom Perls, Director
of the New England Centenarian Study, is actively
tracking about 150 centenarians. His group includes
only one Supercentenarian. By contrast, the GRG has
chosen not to track people who are “merely” 100 years
old, simply because there are literally hundreds of
thousands of them.

The next goal of the GRG is not only
to gather
historical biomedical information, but to do a standard
blood-chemistry laboratory analysis. Ultimately, we
will need to perform a routine DNA analysis. The cost
of DNA sequencing is still too expensive today, but in

about five years, the price will come down to about
$1,000 per patient. That will be a reasonable target,
enabling us to apply to a medical foundation or the
NIA for a grant to allow us to preserve tissue samples
and do DNA sequencing on the people included in our
database.

I am embarrassed to admit that we do
not even have
standard autopsy data on the people in the database.
Typically, the family is not predisposed toward having
a formal autopsy performed. Basically, from their point
of view, their relatives are going to die of “old age,”
and the families see no need for further obscure
medical details. Furthermore, there is typically no
forensic basis for doing an autopsy. Nevertheless, the
GRG would like to know which tissues, like the hair
cells from the inner ear or the rods-and-cones of the
retina, age more rapidly on average; we should be able
to learn a great deal of medically useful information,
since many of these people are blind or deaf or both.

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What has been the source of funding for your
organization?

All of the work is done on a volunteer
basis. We
have taken in some small tax-deductible donations over
the years, in the range of a few hundred dollars.
However, we have not yet been able to obtain a grant
of the sort that we would need to do the types of
studies described above. Without any funding, though,
we have been able to create the database, which is
proving to be a valuable statistical resource in itself,
due to the dedicated efforts of our volunteer committee
members.

How did you become interested in the field of aging?

I have taken it upon myself to become
a self-appointed custodian of all aspects of Anti-Aging
Medicine. I spend almost all of my time doing
theoretical studies and analysis, rather than bench-style
laboratory research. My primary interest is in stem-cell
biology, because that is where I believe the future
payoff will be. In my opinion, if you were to list the
things that gerontologists study today in the laboratory,
I believe that someday you will be disappointed to
discover that it was all largely irrelevant.

I attended a major International
Conference on
Gerontology (IABG-10) held at Cambridge University
at the end of September. The conference was organized
by Dr. Aubrey de Grey, who is a fellow member of the
Editorial Board of this journal, and who contributes
original articles on a regular basis. Aubrey hosted
about 270 people from 27 countries for a four-day
meeting that was the most wonderful gerontology
meeting that I have ever attended. There were
presentations by world-famous scientists covering
almost every aspect of gerontology. I have to admit,
though, that, in my opinion, almost all of the technical
information presented was essentially useless, because
it will soon be deemed obsolete. We are all like the
famous blind men who are trying to feel the true shape
of an elephant without a clue as to what the beast really
looks like.

I would like to propose what I believe
to be an even
better metaphor than the mythological blind men and
the elephant — that of a doctor trying to save the life
of a pregnant woman who

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has just given
birth to a normal baby and is now
suffering a life-threatening hemorrhage. She is losing
blood so fast that she will surely die unless she gets a
transfusion quickly. This was a real problem for
doctors in the 1700s, who witnessed such events with
great regularity and were helpless to do anything about
it. In the early 1800’s, someone thought that maybe
doing blood replacement could be useful. At Oxford
University, members of the local Philosophical Society
(philosophers, it seems, were more empirically active
in those days) discovered that if you replaced the blood
of a dog with the blood of a second dog, sometimes the
recipient dog would turn out to be fine and would
recover fully. But sometimes the dog would die almost
immediately of shock. They did not have a clue as to
why this happened. They reasoned, however, that
maybe if it worked sometimes, it would be worth
trying in humans. So a British doctor tried this
procedure in the case of a woman who gave birth and
then began to hemorrhage. They used the blood of her
husband (for want of a better volunteer donor) to
replace some of the lost blood of the mother following
childbirth. When the results were in, after multiple
attempts at blood replacement, some of the women got
better and wound up perfectly healthy, while in other
cases, the procedure failed catastrophically and the
women died. The delivery doctor had no clue as to why
the procedure worked sometimes but not others. (A
lack of understanding of the absolute requirement for
sterile technique was an important factor that
contributed to the long-term failure of the procedure,
even if you the physician was lucky enough to have a
good “cross match,” which happens about half the time
just by chance, depending on the distribution of the
ABO types in the local population). Finally, laws were
passed forbidding the use of transfusions for human
patients in virtually every western European country.
In retrospect, given the deplorable state of our
knowledge, such prohibitions were not unreasonable.

Then, around the year 1900, a
discovery was made,
which was published in German in an obscure medical
journal but finally translated into English in New York
about the year 1910. The medical appreciation of this
discovery of

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blood
compatibility led to our initial understanding of
the ABO blood-typing system. During World War I, it
became very important to learn how to do transfusions
quickly, efficiently, and under non-sterile battlefield
conditions. Today, we do transfusions routinely.
During the relatively short span of 200 years, we went
through a transition from not knowing anything about
how to do a transfusion safely to being able to do it
routinely. In fact, we would now charge a doctor with
medical malpractice if he/she did not do it correctly!
The ability to understand the ABO system back in the
early 1900’s required having an appreciation of events
that were taking place at a microscopic/molecular
level. There was no way to solve the problem without
that knowledge.

Today, I believe that we in the field of
gerontology
are in a similar situation. We find ourselves in
circumstances similar to the surgeon in 1800, who was
trying to figure out if the husband’s blood would work.
There are things that we just don’t know. In the 1800’s,
some “experts” I am sure proposed that the secret to
success lay in the “color” of the blood, whereas others
suggested the “taste,” and a third group probably
claimed that it was the “smell.”

At the Conference this past September,
many
different groups argued passionately that they had the
answer to aging. Unfortunately, we don’t know what it
is that we don’t know. One of my missions is to
educate people about what we don’t know, how close
we are to knowing what we don’t know, what we
should still try to know, and what we should forget
about trying to know because it is just not going to
happen in our lifetimes. We need to make judgment
calls about how to spend scarce resources to figure out
the things that are currently unknown. We need to
decide what we need to know to carry out our mission
and what could be knowable in the next five to ten
years, assuming the proper expenditure of resources.
This brings us to the topics of the genetics of aging and
stem cells. That is where I have focused my personal
resources and effort.

I first became interested in gerontology
during the
Summer of 1960. I audaciously formed an
organization, with three other friends, to study Anti-Aging Medicine. We optimistically wrote
many white
papers.

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We wrote to Sir Arthur Clarke for his advice, and he
wrote back from Sri Lanka wishing us luck. That
organization has not really had an independent
existence, but that is when my interest began. I have
attempted to build up a perspective on what people
have tried and not tried, and what has worked and not
worked. My final analysis is that we are going to have
to do an experiment that has never been done in nature
before in any species — to allow stem cells to become
active in the context of an adult body, whether it be in
a dog, a cat, a mouse, or a rat. We have to perform this
experiment in order to find the signals that turn on in
situ stem cells in the adult body — stem cells that will
allow the regeneration of new tissue, whether that be a
new liver, pancreas, kidney, lung, heart, brain, etc.
Nature has never done this in an adult. Only during
embryogenesis does nature fabricate brand new organs.
We are presently unable to turn on adult stem cells and
have them create de novo organs in our bodies.

The first doctor who tries this
experiment and does it
badly will find that he or she may have created a
teratoma, a tumor that occasionally forms in the body
in which a new embryo develops in an ectopic place.
When you remove a teratoma surgically, you will find
every tissue-type represented (bones, hair, teeth, and so
forth), with all of the tissues mixed up, randomly, in a
confused pattern. The normal architecture of the tissue
has been obliterated. The worst thing one could
possibly imagine would be the creation of thousands of
teratomas while we are really trying to rejuvenate
tissues.

We need to learn how to stimulate
adult stem cells
throughout the body to recapitulate organogenesis in
the context of adult tissues. That is, we want to
rejuvenate existing tissues while preserving the
architecture of adult tissue. To be able to do this, we
need to find the cytokines that turn on our adult stem
cells. Stem cells are essentially ignorant — they seem
to become activated only when an injury occurs. This
ability of the body to heal itself as a result of an injury
is largely due to the presence of stem cells in the
tissues. The stem cells are there, waiting for the time
when they are needed to take care of a potential
problem. However, if I were to cut your arm off, you

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would not be
able to grow a new arm. A salamander,
on the other hand, is able to grow a new tail. It is that
secret in salamanders vs. humans that we need to
understand. We need to identify the molecules that turn
on such stem cells.

I predict that within the next five to ten
years we
will have compiled a complete catalog of all the signals
for both embryonic and adult stem cells; we will have
identified and characterized all of the cytokines that
turn them on. We will then be able to stimulate a stem
cell to become any particular type of tissue at will in
situ. Adult stem cells are present, mostly in the bone
marrow, waiting for the proper commands to trigger
them to migrate and differentiate into specific types of
tissues.

We need to learn not only the signals
that turn them
on, but also the signals that turn them off. Our
immediate goal in Anti-Aging Medicine is to learn the
full set of commands needed to regulate the adult stem
cells that are already present in our bodies, while
avoiding the predicament illustrated in the story of The
Sorcerer’s Apprentice. The apprentice knows just
enough to be dangerous. He can turn things on, but he
needs the help of the sorcerer to stop a runaway
process that could get out of control. The commands
are all there, written in the “Book of Life,” a text
composed of the letters “A,” “T,” “C,” and
“G,”
otherwise known as DNA. We do not have to invent
any new commands. We just need a Rosetta Stone to
read the language. So, let’s get reading!

Thank you, Dr. Coles

—Interview by Vicki Glaser

NOTE ADDED IN PRESS:

After this interview
was conducted, Dr. Coles was appointed General Chairman of the Program Committee for the
Primedia Annual Conferences on Longevity Medicine to be held in Miami, FL in
September 2004 and Las Vegas, NV
in October 2004. Visit the Committee’s website for further details at
www.antiagingconference.com.